1Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
2Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
3Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
4Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
Copyright © 2022 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
This study was approved by the institutional review board of (blinded for review) (IRB No. B-2105-682-103). All procedures performed were in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Author Contributions
Conceived and designed the analysis: Kang E, Kim EK, Shin HC.
Collected the data: Kim SM, Jang M, Yun BL, Park SY.
Contributed data or analysis tools: Yoon KH, Park Y.
Performed the analysis: Yoon KH, Park Y.
Wrote the paper: Yoon KH, Park Y.
Critical revision of the manuscript for important intellectual content: Kim JH, Kim SH, Suh KJ.
Study supervision: Shin HC.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
CI, confidence interval; CT, chemotherapy; DCIS, ductal carcinoma in situ; ER, estrogen receptor; ER−, estrogen receptor negative; ERhigh, estrogen receptor high positive; ERlow, estrogen receptor low positive; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; HT, hormonal therapy; IDC, invasive ductal carcinoma; LVI, lymphovascular invasion; PR, progesterone receptor.
Clinicopathological characteristics according to ER expression in early breast cancer patients
ER | p-value | ||||||
---|---|---|---|---|---|---|---|
|
| ||||||
ER− (n=454) | ERlow (n=54) | ERhigh (n=1,654) | Total (n=2,162) | Total | ERlow vs. ER− | ERlow vs. ERhigh | |
Age (yr) | |||||||
| |||||||
Mean±SD | 54.0±11.1 | 48.9±10.5 | 51.2±11.0 | 51.7±11.1 | < 0.001 | 0.001 | 0.570 |
| |||||||
Median (range) | 54 (25–85) | 49 (29–72) | 49 (25–88) | 50 (25–88) | |||
| |||||||
Sex | |||||||
| |||||||
Female | 454 (100) | 54 (100) | 1,644 (99.4) | 2,152 (99.5) | 0.326 | - | > 0.99 |
| |||||||
Male | 0 | 0 | 10 (0.6) | 10 (0.5) | |||
| |||||||
Operation | |||||||
| |||||||
Breast conserving surgery | 281 (61.9) | 30 (55.6) | 1,217 (73.6) | 1,528 (70.7) | < 0.001 | 0.366 | 0.003 |
| |||||||
Total mastectomy | 173 (38.1) | 24 (44.4) | 437 (26.4) | 634 (29.3) | |||
| |||||||
Axillary dissection | |||||||
| |||||||
Not done | 40 (8.8) | 9 (16.7) | 299 (18.1) | 348 (16.1) | < 0.001 | 0.130 | 0.482 |
| |||||||
Sentinel lymph node biopsy | 399 (87.9) | 43 (79.6) | 1,324 (80.0) | 1,766 (81.7) | |||
| |||||||
Axillary lymph node dissection | 15 (3.3) | 2 (3.7) | 31 (1.9) | 48 (2.2) | |||
| |||||||
Size (cm) | |||||||
| |||||||
Mean±SD | 1.0±0.7 | 0.8±0.6 | 1.2±0.6 | 1.1±0.6 | < 0.001 | 0.010 | < 0.001 |
| |||||||
Median (range) | 1.1 (0.1–2.0) | 0.6 (0.1–2.0) | 1.2 (0.0–2.0) | 1.1 (0.0–2.0) | |||
| |||||||
Type | |||||||
| |||||||
Ductal carcinoma in situ | 86 (18.9) | 13 (24.1) | 457 (27.6) | 556 (25.7) | 0.001 | 0.404 | 0.870 |
| |||||||
Invasive ductal carcinoma | 357 (78.6) | 39 (72.2) | 1,131 (68.4) | 1,527 (70.6) | |||
| |||||||
Others | 11 (2.4) | 2 (3.7) | 66 (4.0) | 79 (3.7) | |||
| |||||||
T category | |||||||
| |||||||
Tis | 86 (18.9) | 13 (24.1) | 457 (27.6) | 556 (25.7) | < 0.001 | 0.270 | < 0.001 |
| |||||||
T1mic | 81 (17.8) | 13 (24.1) | 81 (4.9) | 175 (8.1) | |||
| |||||||
T1a | 41 (9.0) | 6 (11.1) | 117 (7.1) | 164 (7.6) | |||
| |||||||
T1b | 56 (12.3) | 8 (14.8) | 325 (19.6) | 389 (18.0) | |||
| |||||||
T1c | 190 (41.9) | 14 (25.9) | 647 (40.7) | 878 (40.6) | |||
| |||||||
N category | |||||||
| |||||||
Nx | 41 (9.0) | 8 (14.8) | 297 (18.0) | 346 (16.0) | < 0.001 | 0.249 | 0.904 |
| |||||||
N0 | 408 (89.9) | 45 (83.3) | 1,311 (79.3) | 1,764 (81.6) | |||
| |||||||
N1mic | 5 (1.1) | 1 (1.9) | 46 (2.8) | 52 (2.4) | |||
| |||||||
Stage | |||||||
| |||||||
0 | 86 (18.9) | 13 (24.1) | 457 (27.6) | 556 (25.7) | < 0.001 | 0.579 | 0.877 |
| |||||||
IA | 363 (80.0) | 40 (74.1) | 1,152 (69.6) | 1,555 (71.9) | |||
| |||||||
IB | 5 (1.1) | 1 (1.9) | 45 (2.7) | 51 (2.4) | |||
| |||||||
Grade | |||||||
| |||||||
G1 | 3 (0.7) | 5 (9.3) | 418 (25.3) | 426 (19.7) | < 0.001 | < 0.001 | 0.017 |
| |||||||
G2 | 88 (19.4) | 17 (31.5) | 513 (31.0) | 618 (28.6) | |||
| |||||||
G3 | 221 (48.7) | 12 (22.2) | 200 (12.1) | 433 (20.0) | |||
| |||||||
Unknown | 142 (31.3) | 20 (37.0) | 523 (31.6) | 685 (31.7) | |||
| |||||||
Lymphovascular invasion | |||||||
| |||||||
Present | 41 (9.0) | 1 (1.9) | 184 (11.1) | 226 (10.5) | 0.055 | 0.057 | 0.056 |
| |||||||
Absent | 284 (62.6) | 31 (57.4) | 959 (58.0) | 1,274 (58.9) | |||
| |||||||
Unknown | 129 (28.4) | 22 (40.7) | 511 (30.9) | 662 (30.6) | |||
| |||||||
Progesterone receptor | |||||||
| |||||||
Positive | 16 (3.5) | 22 (40.7) | 1,491 (90.1) | 1,529 (70.7) | < 0.001 | < 0.001 | < 0.001 |
| |||||||
Negative | 438 (96.5) | 32 (59.3) | 163 (9.9) | 633 (29.3) | |||
| |||||||
HER2 | |||||||
| |||||||
Negative | 102 (22.5) | 9 (16.7) | 584 (35.3) | 695 (32.1) | < 0.001 | 0.269 | < 0.001 |
| |||||||
Equivocal | 0 | 0 | 4 (0.2) | 4 (0.2) | |||
| |||||||
Positive | 66 (14.5) | 12 (22.2) | 71 (4.3) | 149 (6.9) | |||
| |||||||
Not done | 286 (63.0) | 33 (61.1) | 995 (60.2) | 1,314 (60.8) | |||
| |||||||
Ki-67 (%) | |||||||
| |||||||
Mean±SD | 26.7±19.0 | 18.1±13.9 | 9.1±9.0 | 13.0±13.9 | < 0.001 | < 0.001 | < 0.001 |
| |||||||
Median (range) | 20 (0–90) | 15 (5–60) | 5 (0–70) | 7 (0–90) | |||
| |||||||
Radiotherapy | |||||||
| |||||||
Done | 263 (57.9) | 27 (50.0) | 1,138 (68.8) | 1,428 (66.0) | < 0.001 | 0.508 | 0.009 |
| |||||||
Not done | 186 (38.8) | 25 (46.3) | 488 (29.5) | 689 (31.9) | |||
| |||||||
Unknown | 15 (3.3) | 2 (3.7) | 28 (1.7) | 45 (2.1) | |||
| |||||||
Hormonal therapy | |||||||
| |||||||
Done | 20 (4.4) | 37 (68.5) | 1,441 (87.1) | 1,498 (69.3) | < 0.001 | < 0.001 | < 0.001 |
| |||||||
Not done | 434 (95.6) | 17 (31.5) | 213 (12.9) | 664 (30.7) | |||
| |||||||
Chemotherapy | |||||||
| |||||||
Done | 242 (53.3) | 21 (38.9) | 373 (22.6) | 636 (29.4) | < 0.001 | 0.045 | 0.005 |
| |||||||
Not done | 212 (46.7) | 33 (61.1) | 1,281 (77.4) | 1,526 (70.6) | |||
| |||||||
Recurrence | |||||||
| |||||||
Yes | 44 (9.7) | 4 (7.4) | 84 (5.1) | 132 (6.1) | 0.001 | 0.587 | 0.357 |
| |||||||
Local | 16 (3.5) | 2 (3.7) | 34 (2.1) | 52 (2.4) | |||
| |||||||
Regional | 7 (1.5) | 0 | 5 (0.3) | 12 (0.6) | |||
| |||||||
Systemic | 13 (2.9) | 1 (1.9) | 21 (1.3) | 35 (1.6) |
Values are presented as number (%) unless otherwise indicated. ER, estrogen receptor; ER−, estrogen receptor negative; ERhigh, estrogen receptor high positive; ERlow, estrogen receptor low positive; HER2, human epidermal growth factor receptor 2; SD, standard deviation.
Cox regression model for risk factors of recurrence in early breast cancer
Total | DCIS | IDC | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
| ||||||||||
Univariate | Multivariate | Univariate | Multivariate | Univariate | Multivariate | |||||||
|
|
|
|
|
| |||||||
HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | HR (95% CI) | p-value | |
Age (yr) | ||||||||||||
| ||||||||||||
< 50 | Reference | Reference | Reference | Reference | Reference | Reference | ||||||
| ||||||||||||
≥ 50 | 0.51 (0.35–0.73) | < 0.001 | 0.46 (0.32–0.66) | < 0.001 | 0.29 (0.12–0.72) | 0.007 | 0.29 (0.12–0.72) | 0.007 | 0.57 (0.38–0.86) | 0.007 | 0.53 (0.36–0.80) | 0.002 |
| ||||||||||||
Type | ||||||||||||
| ||||||||||||
DCIS | Reference | |||||||||||
| ||||||||||||
IDC | 1.20 (0.80–1.80) | 0.390 | - | - | - | - | - | - | - | - | - | - |
| ||||||||||||
Grade | ||||||||||||
| ||||||||||||
1 | Reference | Reference | Reference | Reference | ||||||||
| ||||||||||||
2 | 2.06 (1.10–3.87) | 0.025 | 1.90 (1.00–3.61) | 0.050 | - | - | - | - | 2.06 (1.10–3.87) | 0.025 | 1.89 (0.99–3.61) | 0.054 |
| ||||||||||||
3 | 3.07 (1.65–5.73) | < 0.001 | 2.18 (1.05–4.52) | 0.036 | - | - | - | - | 3.08 (1.65–5.73) | < 0.001 | 2.12 (0.99–4.54) | 0.052 |
| ||||||||||||
LVI | ||||||||||||
| ||||||||||||
No | Reference | Reference | ||||||||||
| ||||||||||||
Yes | 1.46 (0.90–2.37) | 0.131 | - | - | - | - | - | - | 1.46 (0.90–2.37) | 0.130 | - | - |
| ||||||||||||
ER | ||||||||||||
| ||||||||||||
ERhigh | Reference | Reference | Reference | Reference | Reference | |||||||
| ||||||||||||
ERlow | 1.34 (0.49–3.65) | 0.571 | 0.95 (0.50–1.82) | 0.882 | 1.31 (0.18–9.63) | 0.793 | - | - | 1.36 (0.43–4.33) | 0.606 | 1.09 (0.29–4.14) | 0.897 |
| ||||||||||||
ER− | 1.96 (1.35–2.85) | < 0.001 | 0.94 (0.34–2.64) | 0.907 | 0.74 (0.23–2.46) | 0.626 | - | - | 2.29 (1.52–3.44) | < 0.001 | 1.27 (0.36–4.44) | 0.707 |
| ||||||||||||
PR | ||||||||||||
| ||||||||||||
Positive | Reference | Reference | Reference | Reference | ||||||||
| ||||||||||||
Negative | 1.20 (1.00–1.43) | 0.054 | - | - | 0.81 (0.48–1.37) | 0.426 | - | - | 1.62 (1.09–2.42) | 0.018 | 0.52 (0.21–1.33) | 0.175 |
| ||||||||||||
HER2 | ||||||||||||
| ||||||||||||
Positive | Reference | Reference | ||||||||||
| ||||||||||||
Negative | 0.76 (0.27–2.19) | 0.613 | - | - | - | - | - | - | 0.77 (0.38–1.57) | 0.477 | - | - |
| ||||||||||||
Ki-67 | ||||||||||||
| ||||||||||||
< 14 | Reference | Reference | Reference | Reference | Reference | |||||||
| ||||||||||||
≥ 14 | 1.66 (1.18–2.34) | 0.004 | 1.00 (0.64–1.57) | 0.989 | 1.13 (0.46–2.76) | 0.794 | - | - | 1.79 (1.21–2.64) | 0.003 | 0.99 (0.60–1.65) | 0.971 |
| ||||||||||||
HT | ||||||||||||
| ||||||||||||
No | Reference | Reference | Reference | Reference | Reference | |||||||
| ||||||||||||
Yes | 0.50 (0.35–0.70) | < 0.001 | 0.45 (0.25–0.79) | 0.006 | 0.75 (0.37–1.54) | 0.754 | - | - | 0.40 (0.27–0.59) | < 0.001 | 0.30 (0.12–0.77) | 0.012 |
| ||||||||||||
CT | ||||||||||||
| ||||||||||||
No | Reference | Reference | ||||||||||
| ||||||||||||
Yes | 1.06 (0.73–1.52) | 0.777 | - | - | - | - | - | - | 1.00 (0.67–1.50) | 0.985 | - | - |
CI, confidence interval; CT, chemotherapy; DCIS, ductal carcinoma in situ; ER, estrogen receptor; ER−, estrogen receptor negative; ERhigh, estrogen receptor high positive; ERlow, estrogen receptor low positive; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; HT, hormonal therapy; IDC, invasive ductal carcinoma; LVI, lymphovascular invasion; PR, progesterone receptor.
Values are presented as number (%) unless otherwise indicated. ER, estrogen receptor; ER−, estrogen receptor negative; ERhigh, estrogen receptor high positive; ERlow, estrogen receptor low positive; HER2, human epidermal growth factor receptor 2; SD, standard deviation.
CI, confidence interval; CT, chemotherapy; DCIS, ductal carcinoma